Hematopoietic stem cells present in a bone marrow, and mesencymal stem cells serve to maintain an adult body life by being differentiated over their entire life span into respective blood cells, bones, cartilages, fat cells and the like the supply of which is done by them continuously. Recently, these tissue-specific stem cells were reported to be capable of being differentiated also into the cells of multiple organs (nerve, liver, lung, intestinal tracts, cardiac muscles, muscles and the like) under a certain condition, and it is considered to be very important to understand their proliferation mechanisms also in view of the application to a transplantation therapy and a regenerative medicine.
A large number of attempts have been made heretofore to accomplish an in vitro amplification of a hematopoietic stem cell, and some of them were successful to some extent. In bone marrow stromal cells as considered to form a hematopoietic microenvironment (niche) and regulate proliferation and differentiation of hematopoietic precursor cells via hematopoietic factors and an adhesion molecules. Those reported as the hematopoietic factors produced by the stromal cell are cytokines such as IL-3 and IL-6, SCF, receptor-type tyrosine kinase ligands such as an Flt-3 ligand (Gibson, F. M. et al., Br J Haematol 1995), a differentiation-inhibiting factor Notch ligand jagged-1 (Varnum-Finney, B. et al., Blood 1998).
However, most of the membrane-binding factors and adhesion molecules required for the hematopoiesis described above are considered to be unidentified. While it is impossible to culture a hematopoietic stem cell for a prolonged period only by combining currently known factors with each other, such a culture is possible for a certain time period in the presence of stromal cells which are hematopoiesis-supporting cells, suggesting that the stromal cells may express hematopoiesis-related proteins which have not been identified.